title: Continuous exposure to dizocilpine facilitates escalation of cocaine consumption in male Sprague-Dawley rats.
abstract: BACKGROUND
  Although the escalation of cocaine consumption is a hallmark of cocaine dependence, the neurobiological mechanisms that underlie this change in behavior are not well understood.
  
  
  METHODS
  This study used an extended access version of the drug self-administration procedure to explore how N-methyl-d-aspartate (NMDA) receptors are involved in escalation of cocaine consumption. Male Sprague-Dawley rats (n=59) were first trained to self-administer cocaine (0.33 mg/infusion, i.v.) under a fixed-ratio 1 (FR1) schedule of reinforcement. After training, rats were implanted with subcutaneous osmotic minipumps filled with vehicle or the non-competitive NMDAR antagonist, dizocilpine (0.2 or 0.4 mg/kg/d), and subsequently allowed to self-administer cocaine in 2h or 6h self-administration sessions.
  
  
  RESULTS
  In the 6h groups, vehicle-treated rats escalated cocaine self-administration across 15 self-administration sessions; rats treated with dizocilpine escalated cocaine self-administration at a greater rate and to a greater degree. Rats that self-administered cocaine during 2h sessions did not escalate consumption of cocaine under any treatment condition. Discontinuation of dizocilpine treatment in the 6h access condition led to a substantial decrease in cocaine consumption, down to pre-escalation levels, and then control rates of escalation thereafter. Despite large differences in intake under the FR1 schedule, post-escalation break point under a progressive ratio schedule of reinforcement did not differ between groups.
  
  
  CONCLUSIONS
  These data suggest that glutamate tone through NMDA receptors can play a dynamic role in regulating cocaine intake and escalation of consumption.
authors.affiliation: Department of Psychology, University of Colorado Denver, United States. Electronic address: richard.allen@ucdenver.edu.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Allen
mesh_terms: D000818:Animals; D016739:Behavior, Addictive / Q000139:chemically induced; D003042:Cocaine / Q000008:administration & dosage*; D016291:Dizocilpine Maleate / Q000008:administration & dosage* / Q000633:toxicity; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage* / Q000633:toxicity; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology; D012646:Self Administration
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D003042:Cocaine
keywords: Cocaine; Dizocilpine; Escalation; NMDA; Self-administration